SynthesisBMJ open2017
Comparative safety of antiepileptic drugs for neurological development in children exposed during pregnancy and breast feeding: a systematic review and network meta-analysis.
Synthesis in BMJ open, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 8 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
73 citing papers in PubMed, 8 syntheses or guidelines pooled it, 218 citations in OpenAlex.
- Risk of neurodevelopmental disorders after fetal topiramate exposure: a systematic review.Frontiers in drug safety and regulation · 2026Pooled it
- Neurodevelopmental outcomes after prenatal exposure to lamotrigine monotherapy in women with epilepsy: a systematic review and meta-analysis.BMC pregnancy and childbirth · 2024Pooled it
- Comparative Risk of Major Congenital Malformations With Antiseizure Medication Combinations vs Valproate Monotherapy in Pregnancy.Neurology · 2024Pooled it
- Pooled it
- Pooled it
- Pooled it
- Clinical challenges of glioma and pregnancy: a systematic review.Journal of neuro-oncology · 2018Pooled it
- Headache and pregnancy: a systematic review.The journal of headache and pain · 2017Pooled it
- The Scottish medicines in pregnancy programme: supporting the surveillance of medicines use during pregnancy and assessment of associated clinical outcomes.European journal of clinical pharmacology · 2026Article
- Late Pregnancy Antiseizure Medication Exposure and Offspring Neurodevelopmental Risk: A Multi-Child Cohort Study.Annals of neurology · 2026Article
- Informed consent and contraception when prescribing valproate to individuals of childbearing potential: a quality improvement project.Archives of women's mental health · 2026Article
- Pregnancy, baby, and childhood outcomes from using anti-seizure medication during pregnancy.Communications medicine · 2025Article
- A lesson in embracing uncertainty in early safety signals from the Tsepamo study.AIDS (London, England) · 2025Article
- Paternal Valproate Use and Neurodevelopmental Disorder and Congenital Malformation Risk in Offspring.JAMA network open · 2025Observational
- Trends in Prenatal Exposure to Antiseizure Medications Over the Past Decade: A Nationwide Study.Neurology · 2025Article
- Review
- Pre-pregnancy fertility guidance for women of childbearing age with epilepsy: A scoping review.International journal of nursing studies advances · 2025Review
- Differentiation Defect Into GABAergic Neurons in Cerebral Organoids From Autism Patients.CNS neuroscience & therapeutics · 2025Article
- Neurobehavioral Outcomes of Children with Antenatal Exposure to Antiseizure Medications.Indian journal of pediatrics · 2025Article
- Dosing Optimization of Lamotrigine in Peripregnancy Epilepsy Through PopPK Modelling and Simulation.Drug design, development and therapy · 2025Article
13 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesCompare the safety of antiepileptic drugs (AEDs) on neurodevelopment of infants/children exposed in utero or during breast feeding. DESIGN AND
settingSystematic review and Bayesian random-effects network meta-analysis (NMA). MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were searched until 27 April 2017. Screening, data abstraction and quality appraisal were completed in duplicate by independent reviewers.
participants29 cohort studies including 5100 infants/children.
interventionsMonotherapy and polytherapy AEDs including first-generation (carbamazepine, clobazam, clonazepam, ethosuximide, phenobarbital, phenytoin, primidone, valproate) and newer-generation (gabapentin, lamotrigine, levetiracetam, oxcarbazepine, topiramate, vigabatrin) AEDs. Epileptic women who did not receive AEDs during pregnancy or breast feeding served as the control group. PRIMARY AND SECONDARY OUTCOME MEASURES: Cognitive developmental delay and autism/dyspraxia were primary outcomes. Attention-deficit hyperactivity disorder, language delay, neonatal seizures, psychomotor developmental delay and social impairment were secondary outcomes.
resultsThe NMA on cognitive developmental delay (11 cohort studies, 933 children, 18 treatments) suggested that among all AEDs only valproate was statistically significantly associated with more children experiencing cognitive developmental delay compared with control (OR=7.40, 95% credible interval (CrI) 3.00 to 18.46). The NMA on autism (5 cohort studies, 2551 children, 12 treatments) suggested that oxcarbazepine (OR 13.51, CrI 1.28 to 221.40), valproate (OR 17.29, 95% CrI 2.40 to 217.60), lamotrigine (OR 8.88, CrI 1.28 to 112.00) and lamotrigine+valproate (OR 132.70, CrI 7.41 to 3851.00) were associated with significantly greater odds of developing autism compared with control. The NMA on psychomotor developmental delay (11 cohort studies, 1145 children, 18 treatments) found that valproate (OR 4.16, CrI 2.04 to 8.75) and carbamazepine+phenobarbital+valproate (OR 19.12, CrI 1.49 to 337.50) were associated with significantly greater odds of psychomotor delay compared with control.
conclusionsValproate alone or combined with another AED is associated with the greatest odds of adverse neurodevelopmental outcomes compared with control. Oxcarbazepine and lamotrigine were associated with increased occurrence of autism. Counselling is advised for women considering pregnancy to tailor the safest regimen. TRIAL REGISTRATION NUMBER: PROSPERO database (CRD42014008925).
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.